Anti-DNA and antiphospholipid antibodies in IVIG preparations: in vivo study in naive mice.
Intravenous immunoglobulins (IVIG) are therapeutic preparations of pooled normal polyspecific immunoglobulin G. We investigated the presence and the in vivo pathogenic potential of autoantibodies against phospholipids and DNA in several commercial IVIG preparations. The presence of autoantibodies and their antiidiotypic antibodies in the IVIG preparations was detected by ELISA. Naive mice were actively immunized with either IVIG preparations or pathogenic monoclonal antibodies (mAbs) against cardiolipin (CL) or DNA, in an attempt to induce autoimmune conditions. The mice were tested for the presence of mouse autoantibodies (auto-Abs) and for clinical parameters of autoimmune diseases. We found high levels of auto-Abs against a panel of phospholipids and DNA, as well as their antiidiotypic Abs, in all the IVIGs. Affinity studies pointed to a lower affinity of auto-Abs of IVIG origin to their respective antigens compared to pathogenic mAbs. Mice immunized with pathogenic anti-CL mAb had high levels of antiphospholipid auto-Abs, accompanied by thrombocytopenia, prolonged aPTT, and an increased fetal resorption rate. Mice immunized with pathogenic anti-DNA mAb had elevated anti-DNA and anti-CL auto-Abs, along with a high erythrocyte sedimentation rate, leukopenia, and significant proteinuria. Following immunization with IgGs from IVIG batches, mice developed high levels of auto-Abs against phospholipids and DNA, similar to mice immunized with pathogenic anti-DNA or anti-CL mAbs, but none of the mice expressed the clinical manifestations compatible with the presence of these autoantibodies. We conclude that commercial IVIG preparations contain high levels of antiphospholipid and anti-DNA auto-Abs, as well as their antiidiotypic Abs. Although these Abs induced the generation of mouse auto-Abs upon active immunization, following idiotypic manipulation they did not prove to be pathogenic in vivo.
Krause
I
I
Department of Medicine B, Sheba Medical Center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Hashomer, Israel.
Blank
M
M
Shoenfeld
Y
Y
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000032:analysis; D017153:Antibodies, Anticardiolipin / Q000032:analysis; D000974:Antibodies, Antinuclear / Q000032:analysis*; D017152:Antibodies, Antiphospholipid / Q000032:analysis*; D000911:Antibodies, Monoclonal / Q000276:immunology; D001323:Autoantibodies / Q000032:analysis; D004247:DNA / Q000276:immunology*; D004277:DNA, Single-Stranded / Q000276:immunology; D005260:Female; D006801:Humans; D007114:Immunization; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007128:Immunoglobulin Fragments / Q000276:immunology; D016756:Immunoglobulins, Intravenous / Q000097:blood*; D051379:Mice; D008807:Mice, Inbred BALB C / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D017153:Antibodies, Anticardiolipin; D000974:Antibodies, Antinuclear; D017152:Antibodies, Antiphospholipid; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D004277:DNA, Single-Stranded; D007140:Immunoglobulin Fab Fragments; D007128:Immunoglobulin Fragments; D016756:Immunoglobulins, Intravenous; D004247:DNA